Possible involvement of PI3K/AKT/mTOR signaling pathway in the protective effect of selegiline (deprenyl) against memory impairment following ischemia reperfusion in rat
| Autor: | Hossein Amini-Khoei, Gholam Reza Mobini, Tahmineh Mokhtari, Nader Bagheri, Reza Ahmadi, Elham Saghaei, Milad Sabzevary-Ghahfarokhi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Ischemia Morris water navigation task Hippocampus 030209 endocrinology & metabolism Pharmacology Neuroprotection Brain Ischemia Rats Sprague-Dawley Phosphatidylinositol 3-Kinases 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Endocrinology Memory Selegiline medicine Animals Memory impairment Maze Learning Protein kinase B PI3K/AKT/mTOR pathway Neurons Memory Disorders Endocrine and Autonomic Systems business.industry TOR Serine-Threonine Kinases General Medicine medicine.disease Rats Neuroprotective Agents Neurology business Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery Signal Transduction medicine.drug |
| Zdroj: | Neuropeptides. 77:101942 |
| ISSN: | 0143-4179 |
| DOI: | 10.1016/j.npep.2019.101942 |
| Popis: | Short-term cerebral ischemia led to memory dysfunction. There is a pressing need to introduce effective agents to reduce complications of the ischemia. Involvement of PI3K/AKT/mTOR signaling pathway has been determined in the neuroprotective effect of various agents. Selegiline (deprenyl) possessed neuroprotective properties. In this study global ischemia/reperfusion was established in rats. Selegiline (5 mg/kg for 7 consecutive days) administrated via intraperitoneal route. Possible involvement of PI3K/AKT/mTOR signaling pathway was evaluated using qRT-PCR, immunohistochemistry and histophatologic evaluations in the hippocampus. Spatial memory was evaluated by morris water maze (MWM). Results showed that ischemia impaired the memory and ischemic rats spent more time to find hidden platform in the MWM. Ischemia significantly decreased levels of PI3K, AKT and mTOR in the hippocampus. Histopathologic assessment revealed that the percent of dark neurons significantly increased in the CA1 area of the hippocampus of ischemic rats. Selegiline improved the memory as ischemic rats spent fewer time to find hidden platform in the MWM. Findings showed that selegiline increased the level and expression of PI3K, AKT and mTOR as well as decreased the proportion of dark neurons in the CA1 area of the pyramidal layer of the hippocampus. We concluded that selegiline, partially at least, through increases the expression of PI3K, AKT and mTOR as well as decreases the percent of dark neurons in the hippocampus could improve the memory impairment following the ischemia in rats. |
| Databáze: | OpenAIRE |
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